Under the spotlight


Dr Shivan Pancham

Consultant Haematologist at Birmingham City Hospital, explains the science behind Luspatercept, the drug being clinically trialled for patients with thalassaemia.

Current treatments for thalassaemia for the majority of patients consist of blood transfusions and iron chelation treatment to remove the iron that builds up from the transfused red cells. Bone marrow transplantation is available for a minority of patients due to the toxicity of the procedure and lack of suitable donors. Emerging therapies for thalassaemia are agents to improve haemoglobin (such as Luspatercept) and gene therapy.

What is Luspatercept and how does it work?

The genetic changes in thalassaemia result in reduced haemoglobin production and premature death of the early red cells. The bone marrow which makes red cells is expanded due to ineffective production of red blood cells (RBCs). Various signals control the maturation of RBCs. Some of these signals block the later stages of RBC development; one group of these signals is called the transforming growth factor beta (TGF-beta) family. Luspatercept acts as ‘trap’ for this group and allows development and maturation of RBCs.

What is the evidence that Luspatercept works?

Luspatercept was investigated in a clinical trial (BELIEVE) to look at the effect on haemoglobin, transfusions and side effects. The study was conducted at various centres in England, Italy and Greece. The study was conducted in various stages and the results were published in January 2019. Sixty-four adult patients were enrolled, 33 were non-transfusion-dependent (mean haemoglobin less than 10g/dL) and 31 were transfusion dependent receiving more than 4 units of RBC in 8 weeks. Patients were on the trial for an average of 428 days (21-768).

One half of the patients with non-transfusion-dependent thalassaemia who received the higher doses of Luspatercept had increases in haemoglobin of 1.5g/dL. The majority (80%) with transfusion dependent thalassaemia developed a 20% reduction in transfusions. Better responses were seen in patients who had higher doses of Luspatercept. Some patients had an improvement in levels of liver iron.

How is Luspatercept given?

As a subcutaneous injection every 3 weeks.

What are the side effects?

The most frequent were bone pain, headache, myalgia, arthralgia, musculoskeletal pain, back pain, and injection site pain. These tended to be more noticeable in the first 8 weeks of treatment.

How will Luspatercept be used?

Luspatercept will be used along with other treatment for thalassaemia. The hope is that the improvement in haemoglobin will result in fewer transfusions, lower iron levels and will make patients feel better.

Outstanding questions?

Further studies are always needed with any new treatment. Areas such as the safety profile, the impact on iron chelation, use in paediatrics and which patients will get the most benefit from Luspatercept will need to be determined.


The US Food and Drug Administration has just granted approval of Luspatercept in the United States of America

Next Steps?

Luspatercept is currently going through the approval stages in the UK with the National Institute for Clinical Excellence (NICE).